Titre
Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity.
Type
article
Institution
Externe
Périodique
Genes and Development
Auteur(s)
Hu, Y.F.
Auteure/Auteur
Lüscher, B.
Auteure/Auteur
Admon, A.
Auteure/Auteur
Mermod, N.
Auteure/Auteur
Tjian, R.
Auteure/Auteur
Liens vers les personnes
ISSN
0890-9369[print], 0890-9369[linking]
Statut éditorial
Publié
Date de publication
1990-10
Volume
4
Numéro
10
Première page
1741
Dernière page/numéro d’article
1752
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Publication Status: ppublish
Résumé
Enhancer binding protein AP-4 is a transcription factor that activates both viral and cellular genes by binding to the symmetrical DNA sequence, CAGCTG. Here, we report the molecular cloning and characterization of human AP-4 cDNAs. The deduced amino acid sequence reveals that AP-4 is a helix-loop-helix (HLH) protein. Like other members of this family, the AP-4 HLH motif and the adjacent basic domain are necessary and sufficient to confer site-specific DNA binding. However, unlike other HLH proteins, AP-4 also contains two additional protein dimerization motifs consisting of leucine repeat elements LR1 and LR2. The analysis of various deletion and point mutants for their ability to dimerize in the presence or absence of DNA reveals several unusual features. Although the HLH basic region is sufficient for DNA recognition and binding, dimer formation between different truncated versions of AP-4 in solution requires an intact LR1 or LR2 domain. AP-4 is unable to form heterodimers with other helix-loop-helix family members such as the immunoglobulin enhancer binding factor, E12. In contrast, an AP-4 derivative, delta C222, which lacks LR1 and LR2 but retains an intact HLH, can form heterodimers with E12. Moreover, AP-4 molecules containing LR2 or LR1 are unable to form mixed dimers with carboxy-terminally truncated AP-4 molecules such as delta C222, but retain the ability to form complexes with longer versions of AP-4 that contain LR1 and/or LR2. Our findings strongly suggest that AP-4 contains multiple protein-protein interfaces that function to promote homodimer formation and restrict heterocomplexes. These findings provide a mechanism by which different members of the helix-loop-helix family of transcription factors can form functional dimers in a specific fashion with their appropriate partners to control transcriptional networks during cellular differentiation.
Sujets
PID Serval
serval:BIB_52019A23F870
PMID
Open Access
Oui
Date de création
2008-01-24T09:41:23.471Z
Date de création dans IRIS
2025-05-20T13:43:40Z